Sule Tinaz1, Serageldin Kamel2, Sai S Aravala2, Mine Sezgin3, Mohamed Elfil2, Rajita Sinha4. 1. Yale University School of Medicine, Department of Neurology, Division of Movement Disorders, 15 York St, LCI 710, New Haven, CT 06510, USA; Yale University School of Medicine, Clinical Neurosciences Imaging Center, 789 Howard Ave, New Haven, CT 06519, USA. Electronic address: sule.tinaz@yale.edu. 2. Yale University School of Medicine, Department of Neurology, Division of Movement Disorders, 15 York St, LCI 710, New Haven, CT 06510, USA. 3. Yale University School of Medicine, Department of Neurology, Division of Movement Disorders, 15 York St, LCI 710, New Haven, CT 06510, USA; Istanbul University Faculty of Medicine, Department of Neurology, Millet Street, Fatih, Istanbul 34093, Turkey. 4. Yale School of Medicine, Yale Stress Center, 2 Church St South, Suite 209, New Haven, CT 06519, USA; Yale School of Medicine, Department of Psychiatry, 300 George St, New Haven, CT 06511, USA; Yale School of Medicine, Department of Neuroscience, 333 Cedar St, SHM-L-200, New Haven, CT 06510, USA.
Abstract
BACKGROUND: Parkinson's disease (PD) can present with neuropsychiatric symptoms (here, anxiety, depression, and apathy) at any stage of the disease. We investigated the neural correlates of subclinical neuropsychiatric symptoms in relation to motor and cognitive symptoms in a high-functioning PD cohort. METHODS: Brain morphometry of the cognitively intact, early-stage (Hoehn & Yahr 2) PD group (n = 48) was compared to matched controls (n = 37). Whole-brain, pairwise, resting-state functional connectivity measures were correlated with neuropsychiatric symptom, motor exam, and global cognitive scores of the PD group. RESULTS: Factor analysis of highly collinear anxiety, depression, and apathy scores revealed a single principal component (i.e., composite neuropsychiatric symptom score) explaining 71.6% of variance. There was no collinearity between the neuropsychiatric, motor, and cognitive scores. Compared to controls, PD group showed only subcortical changes including amygdala and nucleus accumbens atrophy, and greater pallidal volume. Reduced functional connectivity in the limbic cortical-striatal circuits and increased functional connectivity between the cerebellum and occipito-temporal regions were associated with a more impaired neuropsychiatric profile. This functional connectivity pattern was distinct from those associated with motor deficits and global cognitive functioning. The individual components of the neuropsychiatric symptoms also exhibited unique connectivity patterns. LIMITATIONS: Patients were scanned in "on-medication" state only and a control group with similar neuropsychiatric symptoms was not included. CONCLUSION: Abnormal functional connectivity of distinct neural circuits is present even at the subclinical stage of neuropsychiatric symptoms in PD. Neuropsychiatric phenotyping is important and may facilitate early interventions to "reorganize" these circuits and delay/prevent clinical symptom onset.
BACKGROUND: Parkinson's disease (PD) can present with neuropsychiatric symptoms (here, anxiety, depression, and apathy) at any stage of the disease. We investigated the neural correlates of subclinical neuropsychiatric symptoms in relation to motor and cognitive symptoms in a high-functioning PD cohort. METHODS: Brain morphometry of the cognitively intact, early-stage (Hoehn & Yahr 2) PD group (n = 48) was compared to matched controls (n = 37). Whole-brain, pairwise, resting-state functional connectivity measures were correlated with neuropsychiatric symptom, motor exam, and global cognitive scores of the PD group. RESULTS: Factor analysis of highly collinear anxiety, depression, and apathy scores revealed a single principal component (i.e., composite neuropsychiatric symptom score) explaining 71.6% of variance. There was no collinearity between the neuropsychiatric, motor, and cognitive scores. Compared to controls, PD group showed only subcortical changes including amygdala and nucleus accumbens atrophy, and greater pallidal volume. Reduced functional connectivity in the limbic cortical-striatal circuits and increased functional connectivity between the cerebellum and occipito-temporal regions were associated with a more impaired neuropsychiatric profile. This functional connectivity pattern was distinct from those associated with motor deficits and global cognitive functioning. The individual components of the neuropsychiatric symptoms also exhibited unique connectivity patterns. LIMITATIONS: Patients were scanned in "on-medication" state only and a control group with similar neuropsychiatric symptoms was not included. CONCLUSION: Abnormal functional connectivity of distinct neural circuits is present even at the subclinical stage of neuropsychiatric symptoms in PD. Neuropsychiatric phenotyping is important and may facilitate early interventions to "reorganize" these circuits and delay/prevent clinical symptom onset.
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